(3H)dihydroalprenolol ((3H)DHA) and (3H)quinuclidinyl benzilate ((3H)QNB) binding activities characteristic of beta-adrenergic and muscarinic cholinergic receptors were identified in intact cultured rabbit corneal epithelial cells. Effectiveness of adrenergic agonists in stimulating cAMP accumulation (isoproterenol greater than epinephrine greater than norepinephrine) and of cholinergic drugs in elevating cGMP (oxotremorine much greater than acetylcholine greater than carbamylcholine) closely paralleled their respective affinities for (3H) DHA and (3H)QNB sites. In conjunction with our previous observations that 8-bromo-cGMP and cholinergic agonists, which elevate cGMP, significantly enhance thymidine and leucine incorporation relative to control cultures, while incorporation is significantly reduced after treatment with dibutyryl cAMP or with catecholamines (response abolished by beta-adrenergic antagonists), which elevate cAMP, these results support our hypothesis that proliferation of the corneal epithelium during healing of epithelial defects is subject to bidirectional influence by cAMP-mediated beta-adrenergic and cGMP-mediated cholinergic "first messengers." Current and projected studies include evaluation of regulatory influences of exogenous agents on receptor number and responsiveness and of interactions between drugs influencing cyclic nucleotide levels and growth.